Vitamin D deficiency in children

Dr. Rim El-RifaiConsultant Paediatrician

Queen Mary’s Hospital for Children

Dangers of Vitamin D deficiency: DOH February

2012Up to ¼ of the population has low levels of

Vitamin D in their blood

The majority of pregnant women do not take Vitamin D supplements

People on lower income can get supplements through the Healthy Start Scheme

Vitamin DA prohormone essential for normal absorption of

calcium from the gut

It occurs Naturally in the body following exposure to UVB sunlight, the body can also synthesize it (from cholesterol)

A group of fat-soluble Secosteroids

In humans, it can be ingested as cholecalciferol (vitamin D3) or ergocalciferol (vitamin D2)

25-hydroxy vitamin DThe 25-hydroxy vitamin D test is the most

accurate way to measure vitamin D level.

In the kidney, 25-hydroxy vitamin D changes into an active form of the vitamin.

Synthesis of Vitamin D

In the skin 7-dehydrocholseterol is converted to vitamin D3In the liver vitamin D is converted to 25-hydroxycholecalciferol, or 25-hydroxyvitamin D (Calcidiol) —abbreviated 25(OH)D: the specific vitamin D metabolite measured in serum to determine a vitamin D status.Part of the calcidiol is converted by the kidneys to 1, 25- dihydroxy vitamin D3 (Calcitriol), the biologically active form of vitamin D.

Calcitriol circulates in the blood, regulating the concentration of Calcium and Phosphate in the bloodstream and promoting the healthy growth and remodeling of bone. Calcidiol is also converted to calcitriol outside of the kidneys for other purposes, such as the proliferation, differentiation and apoptosis of cells; calcitriol also affects neuromuscular function and inflammation.[

Vitamin D deficiency in Children in the UK ADCH 2007 Survey of Paediatricians in the West Midlands in 2001

24 cases of Vit D deficiency under 5 years of age

Overall incidence 7.5 per 100 000

11/24 had bowed legs, presented at around 18 months

6 had hypocalcemic seizures at 6 weeks of age

4 had gross motor delay at 17.7 months of age

All were black African or African-Caribbean

Majority were beastfed

50% of those with convulsions were formula fed suggesting inadequate Vit D content in formula milk

Advised: need to supplement vulnerable groups including pregnant women

Vitamin D deficiency rickets among children in

Canada Paediatricians surveyed between 2002-2004

104 confirmed cases in the study period

Overall annual incidence 2.9 cases per 100 000

Mean age at diagnosis 1.4 yrs

65% lived in urban areas

89% had intermediate or darker skin

94% were breastfed

None of the breast fed babies had received a supplement according to guidelines (400 IU/day)

Maternal risk factors included: limited sun exposure, lack of Vit D from diet, lack of Vitamin supplementation during pregnancy and lactation

AMERICAN ACADEMY OF PEDIATRICSPrevention of Rickets and Vitamin D Deficiency: New Guidelines for Vitamin D Intake, April 2003

Cases of rickets in infants attributable to inadequate vitamin D intake and decreased exposure to sunlight continue to be reported in the United States.

A state of deficiency occurs months before rickets is obvious on physical examination.

Also, it is acknowledged that most vitamin D in older children and adolescents is supplied by sunlight exposure. However, dermatologists and cancer experts advise caution in exposure to sun, especially in childhood, and recommend regular use of sunscreens.

Sunscreens markedly decrease vitamin D production in the skin.

People at risk of Vit D deficiency

all pregnant and breastfeeding women, especially teenagers and young women

infants and young children under 5 years of age

older people aged 65 years and over

people who have low or no exposure to the sun, for example those who cover their skin for cultural reasons, who are housebound or confined indoors for long periods

people who have darker skin, for example people of African, African-Caribbean and South Asian origin

PresentationExtremely variable and dependent on:

ageSeverity of deficiencyUnderlying causes

Ranges from Biochemical to severe bony disease

Rickets in 1st year of lifeThe most rapidly growing bones are : skull, upper

limbs and ribs Craniotabes Widening on cranial sutures Frontal bossing Enlarged swollen epiphyses: particularly wrists Bulging of costo-chondral joints (Rachitic Rosary)

Harrison’s sulcus

Irritability

Hypotonia

Bowing of legs

Frontal bossing

Rachitic Rosary

Enlarged Swollen Epiphyses

Rickets after the first yearGenu Varum, Genu Valgum

Abnormal dentition with enamel hypoplasia

Bone pain

Proxymal myopathy

Genu Valgum and Genu Varum

Severe RicketsIn severe cases resulting from low Calcium:

Tetany

Laryngeal stridor

Paraesthesiae

Convulsions

Respiratory failure

Association of subclinical vitamin D deficiency with severe acute lower

respiratory infection in children

Study of 150 hospitalized Indian children in 2004

Subclinical vitamin D deficiency and non-exclusive breast feeding in the first 4 months of age: significant risk factors for severe acute lower

respiratory infections in Indian children

Causes of Vitamin D deficiency

Poor dietary intake most common in Asian population

Reduced synthesis from sun exposure

Genetic: Vitamin D dependent rickets: AR Hypophosphataemic Rickets: x-linked dominany

Malabsorption: Coeliac disease, Cystic Fibrosis

Renal disease (low 1,25 dihydroxy vitamin D- the most active form)

Liver Disease

Medications such as Anticonvulsants induce hepatic enzymes

Calciopenic: Low Ca• Dietary calcium and vitamin D deficiency

Malabsorption

Lack of sun light

Hepatic disease

Anticonvulsant treatment

Renal disease

1-α hydroxylase deficiency

End organ resistance to vitamin D

Phosphopenic:low PO4Fanconi Syndrome

X-linked hypoposphataemic rickets

Renal tubular acidosis

Ocul-cerebro-renal syndrome (Lowe syndrome)

Osteopenia of prematurity

BiochemicalHypocalcaemia

Hypophosphataemia

Elevated Alkaline Phosphatase

Low 1,25 – Dihydroxy vitamin D

Serum Parathyroid Hormone level may be high

RadiologicallyWidening of growth plate

Fraying, Cupping, and Widening of metaphyses

Pseudo fractures

Signs of secondary hyperparathyroidism : subperiosteal erosion

Other investigationsDepending on underlying cause:

Acidosis

Aminoaciduria

Chronic renal failure

anaemia

TreatmentCalcium, phosphate and vitamin D given in varying

combinations

Underlying abnormalities need to be treated (coeliac disease)

Growth needs to be monitored

In hypophsphataemic rickets large doses of Vitamin D are required

In 1α hydroxylase deficiency or end-organ resistance to vitamin D, 1,25- dihydroxy-cholecalciferol is usually required in significant doses

Regular renal USS is important

TreatmentVitamin D 1,000 to 5,000 μg IV/ day until normal

alkaline phosphatase

Then 10 μg / day and 500 ml/ day of milk for calcium requirements

Exposure to sunlight

Dietary source: oily fish, fortified margarine

Dietary sourcesOily fish

Eggs

Infant formula

Some cereals, dairy products, low fat speads have a small amounts added

Difficult to get sufficient Vitamin D from diet alone

Breast feeding and Vitamin DInfants who are breastfed but do not receive

supplemental vitamin D or adequate sunlight exposure are at increased risk of developing vitamin D deficiency or rickets.

Human milk typically contains a vitamin D concentration of 25 IU/L or less.

The recommended adequate intake of vitamin D cannot be met with human milk as the sole source of vitamin D for the breastfeeding infant.

Formulas and Vitamin DAll infant formulas must have a minimum

vitamin D concentration of 40 IU/100 kcal (258 IU/L of a 20-kcal/oz formula) and a maximum vitamin D concentration of 100 IU/100 kcal (666 IU/L of a 20-kcal/oz formula).

All formulas sold have at least 400 IU/L.

If an infant is ingesting at least 500 mL per day of formula (vitamin D concentration of 400 IU/L), he or she will receive the recommended vitamin D intake of 200 IU per day.

Sunlight Exposure Decreased sunlight exposure occurs:

during the winter and other seasons and when sunlight is attenuated by clouds,

air pollution Lifestyles or cultural practices:

decreased time spent outdoors increase the amount of body surface area covered by clothing when

outdoors. individuals with darker skin pigmentation by the use of sunscreens.

Skin Cancer:

age at which direct sunlight exposure is initiated is more important than the total sunlight exposure over a lifetime in determining the risk of skin cancer. AAP guidelines for decreasing exposure:

infants younger than 6 months should be kept out of direct sunlight, children’s activities that minimize sunlight exposure should be selected, protective clothing as well as sunscreens should be used.

Chief Medical Officers:“A significant proportion of people in the UK

probably have inadequate levels of vitamin D in their blood.

“People at risk of vitamin D deficiency, including pregnant women and children under 5, are already advised to take daily supplements”.

DOH February 2012

National Pharmacy Association

Fact sheet prepared with assistance of DOH in March 2012

Providing advice on the prevention of vitamin D Deficiency in the at risk groups

http://www.npa.co.uk/resources/information-leaflets-and-factsheets/clinical/preventing-vitamin-d-deficiency-in-at-risk-groups/

NPA RecommendationsDaily vitamin D supplementation should be

taken by:

All pregnant and breastfeeding womenBreastfed infants from one month of age if mother

did not take vit D supplements through pregnancyAll children aged 6 mon- 5 years (except who

receive more than 500 ml of formula milk, which is fortified with Vit D)

People aged 65 and overPeople who are not exposed to much sunPeople with darker skinsMedical conditions (GI, renal, liver)Medication (Carbamazepine, phenytoin,

primidone, barbiturates, some anti-HIV medicines

NPA Supplementation guidance

Patient Class Daily supplementation dose of vitamin D

Pregnant or breastfeeding 10 micrograms (440 iu)

Breastfed infants from one month of age if mother did not take vitamin D supplementation during pregnancy

Babies may need supplementation in the form of vitamin drops containing vitamin D

Children aged 6 mon to 5 yrs drinking 500 ml or more of formula milk

None required

Children 6 mon to 5 yrs NOT drinking 500 ml of formula milk

Vitamin drops containing vitamin D

Aged 65 years or all ages with limited exposure to sun

10 micrograms (400 iu)

prognosisExcellent in most children

Dependent on compliance with treatment

Less certain in hypophospahtaemic rickets and severe deformities of the limbs may result